ArticleHypertension (Dallas, Tex. : 1979)2015
Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females.
Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 132 citations in OpenAlex.
- The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis.Purinergic signalling · 2026Review
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- Association Between Different Insulin Resistance Indices and Heart Failure in US Adults With Diabetes Mellitus.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2024Article
- The mineralocorticoid receptor in diabetic kidney disease.American journal of physiology. Renal physiology · 2024Review
- Interplay between caveolin-1 and mineralocorticoid receptor in cardiometabolic disease.The Journal of endocrinology · 2024Review
- Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.International journal of molecular sciences · 2024Review
- Molecular Basis of Cardiomyopathies in Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease.Journal of the American Heart Association · 2024Article
- Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.Biomedicines · 2024Review
- Cardiac macrophage metabolism in health and disease.Trends in endocrinology and metabolism: TEM · 2024Review
- Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.Journal of cardiology · 2024Article
- The role and therapeutic potential of macrophages in the pathogenesis of diabetic cardiomyopathy.Frontiers in immunology · 2024Review
- Understanding Diabetic Cardiomyopathy: Insulin Resistance and Beyond.Heart international · 2024Review
- Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models.Channels (Austin, Tex.) · 2023Review
- Effects of pemafibrate on left ventricular diastolic function in patients with type 2 diabetes mellitus: a pilot study.Diabetology international · 2023Article
- Vascular endothelial mineralocorticoid receptors and epithelial sodium channels in metabolic syndrome and related cardiovascular disease.Journal of molecular endocrinology · 2023Review
- Mineralocorticoid receptor antagonists in cardiovascular translational biology.Cardiovascular endocrinology & metabolism · 2023Review
- Aldosterone: Essential for Life but Damaging to the Vascular Endothelium.Biomolecules · 2023Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Overnutrition and insulin resistance are especially prominent risk factors for the development of cardiac diastolic dysfunction in females. We recently reported that consumption of a Western diet (WD) containing excess fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) for 16 weeks resulted in cardiac diastolic dysfunction and aortic stiffening in young female mice and that these abnormalities were prevented by mineralocorticoid receptor blockade. Herein, we extend those studies by testing whether WD-induced diastolic dysfunction and factors contributing to diastolic impairment, such as cardiac fibrosis, hypertrophy, inflammation, and impaired insulin signaling, are modulated by excess endothelial cell mineralocorticoid receptor signaling. Four-week-old female endothelial cell mineralocorticoid receptor knockout and wild-type mice were fed mouse chow or WD for 4 months. WD feeding resulted in prolonged relaxation time, impaired diastolic septal wall motion, and increased left ventricular filling pressure indicative of diastolic dysfunction. This occurred in concert with myocardial interstitial fibrosis and cardiomyocyte hypertrophy that were associated with enhanced profibrotic (transforming growth factor β1/Smad) and progrowth (S6 kinase-1) signaling, as well as myocardial oxidative stress and a proinflammatory immune response. WD also induced cardiomyocyte stiffening, assessed ex vivo using atomic force microscopy. Conversely, endothelial cell mineralocorticoid receptor deficiency prevented WD-induced diastolic dysfunction, profibrotic, and progrowth signaling, in conjunction with reductions in macrophage proinflammatory polarization and improvements in insulin metabolic signaling. Therefore, our findings indicate that increased endothelial cell mineralocorticoid receptor signaling associated with consumption of a WD plays a key role in the activation of cardiac profibrotic, inflammatory, and growth pathways that lead to diastolic dysfunction in female mice.
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